Novel and selective spiroindoline-based inhibitors of Sky kinase.
نویسندگان
چکیده
We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall.
منابع مشابه
Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension
In an elegant example of bench-to-bedside research, a hypothesis that cells in the outflow pathway actively regulate conventional outflow resistance was proposed in the 1990s and systematically pursued, exposing novel cellular and molecular mechanisms of intraocular pressure (IOP) regulation. The critical discovery that pharmacologic manipulation of the cytoskeleton of outflow pathway cells dec...
متن کاملJAK-STAT pathway and JAK inhibitors: a primer for dermatologists
Background: All cellular events depend upon the DNA synthesis and gene expression involving complex interplay between ligands such as interleukins and interferons, with various cell membrane receptors. These ligand-receptors interactions transmit signals within the cell via numerous signal transduction pathways to affect gene expression. Janus kinase/signal transducer and activator of transcrip...
متن کاملDesigning and Synthesis of Novel Celecoxib Derivatives with Aminosulfonylmethyl and Azidomethyl Substituents as Selective Cyclooxygenase-2 Inhibitors
Introduction: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are used in treating pathologic conditions such as fever, pain and inflammation by inhibiting cyclooxygenase and consequently prostaglandin production. Recently , the discovery of different isoforms of this enzyme, Cyclooxygenase-1 (COX-1) and Cyclooxygense-2 (COX-2), has led to the synthesis and introduction of novel drugs with selec...
متن کاملDesign, Synthesis and Biological Evaluation of Novel Peptide-Like Analogues as Selective COX-2 Inhibitors
A new series of peptide-like derivatives containing different aromatic amino acids andpossessing pharmacophores of COX-2 inhibitors as SO2Me or N3 attached to the para positionof an end phenyl ring was synthesized for evaluation as selective cyclooxygenase-2 (COX-2)inhibitors. The synthetic reactions were based on the solid phase peptide synthesis methodusing Wang resin. One of the analogues, i...
متن کاملInvestigation the Mechanism of Interaction between Inhibitor ALISERTIB with Protein Kinase A and B Using Modeling, Docking and Molecular Dynamics Simulation
The high level of conservation in ATP-binding sites of protein kinases increasingly demandsthe quest to find selective inhibitors with little cross reactivity. Kinase kinases are a recently discovered group of Kinases found to be involved in several mitotic events. These proteins represent attractive targets for cancer therapy with several small molecule inhibitors undergoing different ph...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Bioorganic & medicinal chemistry letters
دوره 22 1 شماره
صفحات -
تاریخ انتشار 2012